Suitability of the ICH S1B(R1) Weight-of-Evidence Framework to Evaluate Glucagon-Like Protein-1 Receptor Agonist (GLP-1RA) Carcinogenicity Risk. (PubMed, Regul Toxicol Pharmacol) - Sep 27, 2026 - "Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are an established treatment for management of type 2 diabetes mellitus (T2DM) and obesity...This manuscript applies that framework across seven approved GLP-1RAs: lixisenatide, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, and albiglutide, to evaluate the relevance of rodent thyroid tumors and the utility of 2-year bioassays for this drug class. Across all six WoE domains, the evidence supports concluding that GLP1-RAs are tumorigenic in rats via a known human-irrelevant mechanism. Thus, within the S1B(R1) WoE framework, future carcinogenicity testing in rats is unlikely to provide additional value for regulatory decision-making for this class of pharmaceuticals."
Journal • Cerebral Hemorrhage • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Type 2 Diabetes Mellitus
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Alex G Gauthier; Brigitte Cronin; Denali Boon; Isaac Mohar; Katherine A Roach; Manoochehr Khazaee
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